Long‐term follow‐up of 64 children with classical infantile‐onset Pompe disease since 2004: A French real‐life observational study.

Background: Classical infantile‐onset Pompe disease (IOPD) is the most severe form of Pompe disease. Enzyme replacement therapy (ERT) has significantly increased survival but only a few studies have reported long‐term outcomes. Methods: We retrospectively analyzed the outcomes of classical IOPD patients diagnosed in France between 2004 and 2020. Results: Sixty‐four patients were identified. At diagnosis (median age 4 months) all patients had cardiomyopathy and most had severe hypotonia (57 of 62 patients, 92%). ERT was initiated in 50 (78%) patients and stopped later due to being ineffective in 10 (21%). Thirty‐seven (58%) patients died during follow‐up, including all untreated and discontinued ERT patients, and 13 additional patients. Mortality was higher during the first 3 years of life and after the age of 12 years. Persistence of cardiomyopathy during follow‐up and/or the presence of heart failure were highly associated with an increased risk of death. In contrast, cross‐reactive immunologic material (CRIM)‐negative status (n = 16, 26%) was unrelated to increased mortality, presumably because immunomodulation protocols prevent the emergence of high antibody titers to ERT. Besides survival, decreased ERT efficacy appeared after the age of 6 years, with a progressive decline in motor and pulmonary functions for most survivors. Conclusions: This study reports the long‐term follow‐up of one of the largest cohorts of classical IOPD patients and demonstrates high long‐term mortality and morbidity rates with a secondary decline in muscular and respiratory functions. This decreased efficacy seems to be multifactorial, highlighting the importance of developing new therapeutic approaches targeting various aspects of pathogenesis. [ABSTRACT FROM AUTHOR]